Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wa have previously reported that insulin accelerates recovery of intracellular Ca2+ concentrations ([Ca2+]i) from pressor agonist-induced Ca2+ loads and stimulates both plasmalemmal and sarcoplasmic-reticulum Ca(2+)-ATPase gene expression in cultured and freshly isolated vascular smooth-muscle cells (VSMCs), suggesting that insulin attenuation of vascular tone may result from modulation of [Ca2+]i. Accordingly, we have now evaluated the linkage between this insulin-regulation of VSMC[Ca2+]i and classical actions of insulin (i.e. glucose transport and metabolism). Cultured VSMCs were incubated in the presence or absence of insulin in a medium containing either pyruvate, glucose, 3-O-methylglucose or 2-deoxyglycose. Insulin caused an 87% increase in [Ca2+]i recovery rate after stimulation with arginine-vasopressin (P < 0.01) and caused a marked increase in Ca(2+)-ATPase mRNA and protein levels in the presence of glucose. Comparable increases in both [Ca2+]i recovery and Ca2(+)-ATPase expression were found when glucose was replaced by 2-deoxyglucose. In contrast, no stimulation was found in either the glucose-free or 3-O-methylglucose-containing medium. As both glucose analogues are transported, but only 2-deoxyglucose is phosphorylated, this indicates that glucose transport and metabolism to glucose 6-phosphate is essential for insulin regulation of VSMC [Ca2+]i, possibly via a glucose-6-phosphate-dependent carbohydrate-response element in the Ca2(+)-ATPase gene.
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PMID:Insulin stimulation of intracellular free Ca2+ recovery and Ca(2+)-ATPase gene expression in cultured vascular smooth-muscle cells: role of glucose 6-phosphate. 748 95

Physiologically, a postprandial glucose rise induces metabolic signal sequences that use several steps in common in both the pancreas and peripheral tissues but result in different events due to specialized tissue functions. Glucose transport performed by tissue-specific glucose transporters is, in general, not rate limiting. The next step is phosphorylation of glucose by cell-specific hexokinases. In the beta-cell, glucokinase (or hexokinase IV) is activated upon binding to a pore protein in the outer mitochondrial membrane at contact sites between outer and inner membranes. The same mechanism applies for hexokinase II in skeletal muscle and adipose tissue. The activation of hexokinases depends on a contact site-specific structure of the pore, which is voltage-dependent and influenced by the electric potential of the inner mitochondrial membrane. Mitochondria lacking a membrane potential because of defects in the respiratory chain would thus not be able to increase the glucose-phosphorylating enzyme activity over basal state. Binding and activation of hexokinases to mitochondrial contact sites lead to an acceleration of the formation of both ADP and glucose-6-phosphate (G-6-P). ADP directly enters the mitochondrion and stimulates mitochondrial oxidative phosphorylation. G-6-P is an important intermediate of energy metabolism at the switch position between glycolysis, glycogen synthesis, and the pentose-phosphate shunt. Initiated by blood glucose elevation, mitochondrial oxidative phosphorylation is accelerated in a concerted action coupling glycolysis to mitochondrial metabolism at three different points: first, through NADH transfer to the respiratory chain complex I via the malate/aspartate shuttle; second, by providing FADH2 to complex II through the glycerol-phosphate/dihydroxy-acetone-phosphate cycle; and third, by the action of hexo(gluco)kinases providing ADP for complex V, the ATP synthetase. As cytosolic and mitochondrial isozymes of creatine kinase (CK) are observed in insulinoma cells, the phosphocreatine (CrP) shuttle, working in brain and muscle, may also be involved in signaling glucose-induced insulin secretion in beta-cells. An interplay between the plasma membrane-bound CK and the mitochondrial CK could provide a mechanism to increase ATP locally at the KATP channels, coordinated to the activity of mitochondrial CrP production. Closure of the KATP channels by ATP would lead to an increase of cytosolic and, even more, mitochondrial calcium and finally to insulin secretion. Thus in beta-cells, glucose, via bound glucokinase, stimulates mitochondrial CrP synthesis. The same signaling sequence is used in the opposite direction in muscle during exercise when high ATP turnover increases the creatine level that stimulates mitochondrial ATP synthesis and glucose phosphorylation via hexokinase. Furthermore, this cytosolic/mitochondrial cross-talk is also involved in activation of muscle glycogen synthesis by glucose. The activity of mitochondrially bound hexokinase provides G-6-P and stimulates UTP production through mitochondrial nucleoside diphosphate kinase. Pathophysiologically, there are at least two genetically different forms of diabetes linked to energy metabolism: the first example is one form of maturity-onset diabetes of the young (MODY2), an autosomal dominant disorder caused by point mutations of the glucokinase gene; the second example is several forms of mitochondrial diabetes caused by point and length mutations of the mitochondrial DNA (mtDNA) that encodes several subunits of the respiratory chain complexes. Because the mtDNA is vulnerable and accumulates point and length mutations during aging, it is likely to contribute to the manifestation of some forms of NIDDM.(ABSTRACT TRUNCATED)
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PMID:Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the cellular energy circuit. 854 53

Red cell metabolism (RCM) was examined in 63 patients with severe and complicated meningococcal infection and purulent meningitis of another etiology. There were complex pathobiochemical shifts with changes in glycolysis (in activity of lactate dehydrogenase, piruvatkinase, in the amount of piruvate, lactate and 2,3-DPG), antioxidant status (in the activity of glucose-6-phosphate-dehydrogenase, glutathione reductase), Mg+2, Na+, K(+)-dependent ATPase. Primary depression of red cell metabolism changed for compensatory activation for hypoxia adaptation in clinical improvement. RCM disturbance coincided with emergence of early complications and reached maximum in lethal outcome. Pathogenetic and clinical implications of RCM in meningococcal infection and purulent meningitis are described.
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PMID:[The enzyme activity and pyruvate, lactate and 2,3-DPG levels in the erythrocytes of patients with severe forms of meningococcal infection and suppurative meningitis]. 877 62

Microsomes prepared from three rat tissues were examined for their ability to import glucose-6-phosphate (G-6-P). Microsomes from liver, which possess a high level of glucose-6-phosphatase activity, were compared with those from cerebral cortex and cardiac muscle, which are not involved in the export of glucose and in which glucose-6-phosphatase activity is relatively low. In all three, a selective permeability to G-6-P was detected by light scattering. However, the sugar-phosphate specificity of the transport process differed. G-6-P was able to enhance ATP-dependent Ca2+ sequestration in all three types of microsomes. In addition, enzymatic detection of G-6-P after the rapid filtration of microsomes determined that, in the absence of Ca2+ and ATP, a level of intramicrosomal G-6-P approaching a passive equilibrium with the extramicrosomal G-6-P concentration was rapidly achieved in all three tissues. However, under conditions in which Ca2+ was being actively accumulated, the intramicrosomal levels of G-6-P exceeded the equilibrium value by three- to fourfold. This enhanced sequestration was not observed in the presence of Ca2+ or ATP alone or in the presence of a Ca2+ ionophore or an inhibitor of the microsomal Ca2+ ATPase. These data are consistent with a selective import pathway into the endoplasmic/sarcoplasmic reticulum for G-6-P independent of glucose-6-phosphatase activity. In addition, they suggest an alternate explanation for the enhanced sequestration of Ca2+ by the endoplasmic/sarcoplasmic reticulum of intact cells seen when extracellular glucose is increased.
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PMID:Glucose-6-phosphate and Ca2+ sequestration are mutually enhanced in microsomes from liver, brain, and heart. 960 62

Regulation of intracellular Ca2+ ([Ca2+]i) plays a key role in obesity, insulin resistance and hypertension, and [Ca2+]i disorders may represent a fundamental factor linking these three conditions. We have shown insulin to be a direct vasodilator, attenuating voltage-gated Ca2+ influx and stimulating Ca(2+)-ATPase transcription via a glucose-6-phosphate response element. These result in a net decrease in [Ca2+]i and thereby decrease vascular resistance, while these effects are blunted in insulin resistance, leading to increased vascular resistance. Consistent with this concept, pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. While insulin regulates [Ca2+]i, Ca2+ also regulates insulin signaling, as increasing [Ca2+]i impairs insulin signaling in some systems, possibly due to Ca2+ inhibition of insulin-regulated dephosphorylation. Finally, in recent studies of the mouse agouti gene, we have also demonstrated increased [Ca2+]i to play a key role in adipocyte lipogenesis, as follows. We have found dominant agouti mutants to exhibit increased [Ca2+]i in most tissues, leading to increased vascular reactivity and insulin resistance in vascular smooth muscle and skeletal muscle cells, respectively. Further, we have found recombinant agouti protein to directly increase [Ca2+]i in a variety of cells, including murine and human adipocytes, and to stimulate both the expression and activity of adipocyte fatty acid synthase and increase triglyceride accumulation in a Ca(2+)-dependent manner. These effects can be mimicked by stimulation of Ca2+ influx and blocked by Ca2+ channel inhibition, while treatment of mice with a Ca2+ antagonist attenuates agouti-induced obesity. Since humans express agouti in adipose tissue, it may similarly exert paracrine effects on [Ca2+]i and thereby stimulate de novo lipogenesis and promote obesity. Thus, Ca2+ signaling represents a target for therapeutic intervention in obesity as well as hypertension and insulin resistance.
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PMID:Nutritional and endocrine modulation of intracellular calcium: implications in obesity, insulin resistance and hypertension. 982 18

The exact chemical composition of the red blood cell (RBC) membrane may vary depending on the methods used to isolate the membrane. We provide evidence here that RBC membrane can be fractionated by differential centrifugation and/or density gradient centrifugation into two distinct types, designated as 'heavy membrane' (HM) and 'light membrane' (LM). The amount of LM is twice that of HM on a per cell basis. HM and LM differ in some biochemical and electrophoretic properties. The total activities of Na+, K+- and Ca2+-ATPases, superoxide dismutase, glutathione peroxidase, catalase and glucose-6-phosphate and 6-phosphogluconate dehydrogenase are significantly higher in LM than HM on a per cell basis. While there is no significant difference in the specific activity of other enzymes between the two membranes, the specific activity of Ca2+-ATPase is significantly higher in HM, whereas Na+,K+-ATPase activity is higher in LM. There is a remarkable difference in the distribution of major ghost polypeptides between these two membranes. Component I of spectrin, component III and a protein with mol. wt. of 165 KDa are present in smaller amounts, whereas component II of spectrin and proteins with mol. wt. of 145, 84 and 76 KDa, respectively, are present in higher amounts in HM than LM. Some proteins such as band 4.1, 48 and 46 KDa are present only in LM, whereas some proteins with mol. wt. of 96, 78 and 43 KDa, respectively are present only in HM. It has been confirmed that these two membranes are not representatives of either (a) right side-out vs. inside out vesicles, or (b) open vs. sealed membranes. Thus HM and LM are two distinct membrane fractions. It is suggested that some part of the membrane is denser than other parts, and during hemolysis of RBCs, the rbc membrane is spliced resulting in two populations, dense and light.
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PMID:Heterogeneity of human red blood cell membrane: co-existence of heavy and light membranes. 1044 13

The metabolic responses occurring in cucumber (Cucumis sativus L.) roots (a strategy-I plant) grown under iron-deficiency conditions were studied in-vivo using 31P-nuclear magnetic resonance spectroscopy. Iron starvation induced activation of metabolism leading to the consumption of stored carbohydrates to produce the NAD(P)H, ATP and phosphoenolpyruvate necessary to sustain the increased activity of the NAD(P)H:Fe(3+)-reductase, the H(+)-ATPase (EC 3.6.1.35) and phosphoenolpyruvate carboxylase (EC 4.1.1.31). Activation of catabolic pathways was supported by the enhancement of glycolytic enzymes and concentrations of the metabolites glucose-6-phosphate and fructose-6-phosphate, and by enhancement of the respiration rate. Moreover, Fe-deficiency induced a slight increase in the cytoplasmic (pHc) and vacuolar (pHv) pHs as well as a dramatic decrease in the vacuolar phosphate (Pi) concentration. A comparison was done using fusicoccin (FC), a fungal toxin which stimulates proton extrusion. Changes in pHc and pHv were measured after addition of FC. Under these conditions, a dramatic alkalinization of the pHv of -Fe roots was observed, as well as a concomitant Pi movement from the vacuole to the cytoplasm. These results showed that Fe starvation was indeed accompanied by the activation of metabolic processes useful for sustaining the typical responses occurring at the plasma-membrane level (i.e. increases in the NAD(P)H:Fe(3+)-reductase and H(+)-ATPase activities) as well as those involved in the homeostasis of pHc. The decrease in vacuolar Pi levels induced by Fe-deficiency and FC and movement of Pi from the vacuole to the cytoplasm suggest a possible involvement of this compound in the cellular pH-stat system.
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PMID:Metabolic responses in cucumber (Cucumis sativus L.) roots under Fe-deficiency: a 31P-nuclear magnetic resonance in-vivo study. 1087 32

Hexokinase II is an enzyme central to glucose metabolism and glucose repression in the yeast Saccharomyces cerevisiae. Deletion of HXK2, the gene which encodes hexokinase II, dramatically changed the physiology of S. cerevisiae. The hxk2-null mutant strain displayed fully oxidative growth at high glucose concentrations in early exponential batch cultures, resulting in an initial absence of fermentative products such as ethanol, a postponed and shortened diauxic shift, and higher biomass yields. Several intracellular changes were associated with the deletion of hexokinase II. The hxk2 mutant had a higher mitochondrial H(+)-ATPase activity and a lower pyruvate decarboxylase activity, which coincided with an intracellular accumulation of pyruvate in the hxk2 mutant. The concentrations of adenine nucleotides, glucose-6-phosphate, and fructose-6-phosphate are comparable in the wild type and the hxk2 mutant. In contrast, the concentration of fructose-1,6-bisphosphate, an allosteric activator of pyruvate kinase, is clearly lower in the hxk2 mutant than in the wild type. The results suggest a redirection of carbon flux in the hxk2 mutant to the production of biomass as a consequence of reduced glucose repression.
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PMID:Physiological properties of Saccharomyces cerevisiae from which hexokinase II has been deleted. 1128 9

Mannose 6-phosphate receptors (MPRs) deliver lysosomal hydrolases from the Golgi to endosomes and then return to the Golgi complex. TIP47 recognizes the cytoplasmic domains of MPRs and is required for endosome-to-Golgi transport. Here we show that TIP47 also bound directly to the Rab9 guanosine triphosphatase (GTPase) in its active, GTP-bound conformation. Moreover, Rab9 increased the affinity of TIP47 for its cargo. A functional Rab9 binding site was required for TIP47 stimulation of MPR transport in vivo. Thus, a cytosolic cargo selection device may be selectively recruited onto a specific organelle, and vesicle budding might be coupled to the presence of an active Rab GTPase.
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PMID:Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. 1136 Sep 88

A cytochemical method allowing the localization and quantification of plasma membrane Ca2+-ATPase (PMCA) in frozen sections obtained from digestive gland cells of Mytilus galloprovincialis, Tapes tapes and Chamelea gallina, is presented. The method utilizes lead as a trapping agent of PO4(2-) ions released by Ca2+-ATPase activity. The amount of lead sulphide precipitate proportionally related to PMCA activity was quantified by a light microscopy digital imaging analysis system. The optimal assay conditions of Ca2+-ATPase activity evaluated at pH 7.4 were: 200 microM free Ca2+, 200 mM KCl, 2 mM ATP, and under such analysis conditions the enzyme showed a linear trend up to 60 min (at 20 degrees C). The PMCA activity was substrate specific: ADP was utilized only at a low rate (24% with respect to an equimolar ATP concentration), while glucose-6-phosphate and beta-glycerophosphate were poorly hydrolyzed. The enzyme activity was strongly inhibited by sodium ortho-vanadate. Our detection of a Ca2-ATPase activity at nanomolar concentrations of free Ca2+ suggests that we have identified a plasma membrane Ca2-ATPase involved in Ca2+ homeostasis. The Ca2+-ATPase was found to be localized in the basal part of the plasma membrane in the digestive gland cells of Mytilus galloprovincialis and Tapes tapes, but in the apical plasma membrane of Chamelea gallina. The possible implications of the different cellular distributions of PMCA activity is discussed.
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PMID:Cytochemical localization and quantification of plasma membrane Ca2+-ATPase activity in mollusc digestive gland cells. 1204 46


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